The effect of the combined administration of colloids and lactated Ringer's solution on the coagulation system: an in vitro study using thrombelastograph coagulation analysis (ROTEG

Gelatin solutions are often given in clinical practice once the maximal dose of a median-weight hydroxyethyl starch (HES) has been reached. Colloids are usually combined with lactated Ringer's solution (RL). Whether the combined administration of colloids and/or crystalloids affects blood coagulation is not known. We diluted blood by 20%, 40%, and 60% with RL, gelatin (Gelofusin), 6% HES 130/0.4 (Voluven), and 6% HES 200/0.5 (Iso-Hes), as well as with combinations of these solutions at a ratio of 1:1 (gelatin/RL, 6% HES 130/0.4:RL, 6% HES 200/0.5:RL, 6% HES 130/0.4:gelatin, 6% HES 200/0.5:gelatin). Thereafter, blood was analyzed by using modified thrombelastograph coagulation analysis (ROTEG) and clotting time, clot formation time, and maximal clot firmness were determined. RL had the least effect on hemostasis. Gelatin administered alone impaired the coagulation system significantly less than each median-weight HES administered alone. We conclude that gelatin combined with 6% HES 200/0.5 or 6% HES 130/0.4 decreases hemostasis <6% HES 200/0.5 or 6% HES 130/0.4 administered alone. IMPLICATIONS: The effect of the combined administration of different colloids and/or crystalloids on coagulation is not known. We show that hemostasis is less impaired using a combination of gelatin and median-weight starches than using median-weight starches alone. Furthermore, the combination of lactated Ringer's solution and gelatin decreases the coagulation system to the same extent as the combination of lactated Ringer's solution and 6% hydroxyethyl starch 130/0.4.     

In vitro effects of different medium molecular hydroxyethyl starch solutions and lactated Ringer's solution on coagulation using SONOCLOT

Hydroxyethyl starch (HES) solutions are widely used to replace intravascular volume. HES solutions differ from each other with regard to molecular weight and mode of hydroxyl substitution (degree of hydroxylation, C2:C6 hydroxyethyl ratio, concentration), factors which may have varying effects on coagulation. We studied, in vitro, three different HES preparations (molecular weight/degree of hydroxylation/concentration/C2:C6 ratio of substitution 70.000/0. 5/6%/3.2; Pharmacia & Upjohn Co., Erlangen, Germany; 130.000/0. 4/6%/11.2 and 200.000/0.5/6%/4.6; Fresenius Co., Bad Homburg, Germany) and, for comparison, lactated Ringer's solution (RL) at 33% and 66% dilution with whole blood. The influence of hemodilution was measured by using routine laboratory variables and SONOCLOT (Sonoclot II Coagulation and Platelet Function Analyzer, Sienco Co.) analysis, using a viscoelastic test, on the cellular as well as on the plasmatic hemostatic system. For statistical analysis of quantitative data, we used nonparametric analysis of variance and adequate post hoc tests. Qualitative data were analyzed by using the nonparametric Kruskal-Wallis test. A P value below 0.05 was considered significant. In contrast to the control group with RL, the liquid phase of coagulation (activated clotting time) was slightly affected by the 33% diluted HES solutions. HES 70.000, 130. 000, and 200.000 interfered significantly with the early stage of coagulation as expressed by the clot rate (gel/fibrin formation). Clot maturation and speed of maturation (time to peak) were strongly affected by HES 70.000 at all grades of dilution. HES 130.000 showed a faster clot formation process compared with the other HES solutions. HES 130.000 diluted 33% showed a better clot retraction as compared with the other HES solutions. In conclusion, in vitro hemodilution comparing different medium molecular weight HES solutions reveals that HES 130.000 seems preferable regarding some aspects of clot formation and retraction. RL affected clot formation only minimally, except for the early activation of clotting, which was measured by a shortened activated clotting time. IMPLICATIONS: We investigated the effect of different hydroxyethyl starch (HES) solutions (70.000, 130.000, 200.000) on coagulation. Regarding clot formation and retraction, HES 130.000 had some advantages over the other tested HES solutions. Lactated Ringer's solution affected coagulation only minimally, except for the early stage of clot formation.     

The effect of In vitro hemodilution with gelatin, dextran, hydroxyethyl starch, or Ringer's solution on Thrombelastograph

To determine the effects of progressive in vitro hemodilution with various plasma substitutes on whole blood coagulation, blood was obtained from six healthy volunteers. The Thrombelastograph((R)) (TEG; Haemoscope Corp., Morton Grove, IL) variables of reaction time, coagulation time, maximum amplitude, and growth angle were determined. The following plasma substitutes were tested: two gelatin solutions (4% gelatin polysuccinate and 5.5% oxypolygelatin); two dextrans (10% dextran 40 and 6% dextran 60); and five hydroxyethyl starch (HES) preparations (6% HES 70/0.5-0.55, 3% HES 200/0.5, 6% HES 200/0.5, 10% HES 200/0.5, and 6% HES 450/0.7). Ringer's solution was also tested to assist analyzing the intrinsic effect of colloid molecules on blood coagulation. The dilution ratios of citrated blood volume to plasma substitute volume were 10:2, 10:4, and 10:10. Blood coagulation was affected by plasma substitutes when the dilution ratios of citrated blood volume to colloid solution volume were 10:4 and 10:10. TEG variables did not change significantly after in vitro hemodilution with lactated Ringer's solution. The tested gelatin solutions showed less intrinsic effect on blood coagulation than other plasma substitutes. All HES preparations showed similar intrinsic effects as 6% dextran 60. The plasma substitute of 10% dextran 40 had the strongest effect on coagulation. Coagulation time was the most markedly affected TEG variable. Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation, 10% dextran 40 has the strongest effect on coagulation. IMPLICATIONS: Blood coagulation may be compromised when the dilution ratio of blood volume to colloid solution volume is >10:4. Whereas gelatin solutions have less intrinsic effect on blood coagulation than hydroxyethyl starch or dextran, 10% dextran 40 has the strongest effect on coagulation.     

急性扩容性血液稀释电解质的影响

目的对比观察乳酸钠林格液和万汶在术前急性扩容性血液稀释前后电解质的变化。方法20例病人随机分为万汶组(组1)和乳酸钠林格液组(组2)。病人入室开放静脉后分别给予两组液体15 ml/kg,30 min输注完毕。分别于输液前后抽血查血常规、电解质。结果两组扩容前后MAP、HR无明显变化,血K+稀释性降低。组1扩容后HCT下降明显,血Na+明显增加,但仍在正常范围之内。组2扩容后HCT明显下降,血Na+在正常范围之内。结论万汶扩容效果优于乳酸钠林格液,但可致血Na+升高,血K+稀释性降低。     

The effects of perioperatively administered colloids and crystalloids on primary platelet-mediated hemostasis and clot formation

To explore whether routinely administered colloids and crystalloids influence the hemostatic system, we studied 60 patients undergoing knee replacement surgery during randomized intravascular fluid administration using 6% hydroxyethyl starch 200/0.5 (HES) or 4% modified gelatin (GEL) in addition to a basal infusion of lactated Ringer's solution (RL), or exclusively RL. In addition to routine coagulation tests, measurements of coagulation factors were performed. Also, functional measurements of the in vitro bleeding time by use of the platelet function analyzer (PFA-100 and ROTEG analysis (ROTEG(R); extrinsically and intrinsically [Ex; In] activated measurements of clotting time, CT [s]; clot formation time, CFT [s]; clot strength, A20 [mm]; fibrinogen component of the clot, FibA20 [mm]; and maximal clot elasticity) were used. Time dependency of variables was analyzed with a repeated-measures analysis of variance (all groups pooled); differences between groups were detected by comparing the calculated area under the curve (AUC(A-D)). For all variables, except ExCT, ExCFT, and InCFT, a significant time dependency was demonstrated, indicating that impaired platelet-mediated hemostasis and clot formation occurred with IV administration of fluids. Total clot strength, fibrinogen part, and clot elasticity decreased significantly more in the colloid groups than in the RL group (InA20: HES, -13.0 mm; GEL, -11.5 mm; RL, -1.3 mm; P = 0.042; FibA20: HES, -10.5 mm; GEL, -6.0 mm; RL, -1.3 mm: P < 0.0001; MCE: HES, -48; GEL, -35; RL, -15.8; P < 0.0001). The decrease in fibronectin concentrations was significantly smaller with GEL as compared with HES, whereas a weak trend toward a larger decrease in fibrinogen concentrations was observed with both colloids. Results show that colloid administration reduces final clot strength more than does RL alone, which also exhibited effects, albeit minor, on the coagulation system. The reduction in total clot strength was due to impaired fibrinogen polymerization, resulting in a decreased fibrinogen part of the clot and reduced clot elasticity. IMPLICATIONS: Our data suggest that during deliberate colloid administration, critically impaired fibrinogen polymerization and reduced fibrinogen concentrations might be reached earlier than expected. Therefore, maintaining fibrinogen concentrations seems essential when continuing blood loss is bridged by colloid infusion until transfusion triggers are reached, especially in patients already exhibiting borderline fibrinogen levels at baseline.     

An in vitro study comparing the effects of Hextend, Hespan, normal saline, and lactated ringer's solution on thrombelastography and the activated partial thromboplastin time

OBJECTIVE: The purpose of this study was to determine if 6% HES 450/0.7 (hydroxyethyl starch 450/0.7) in normal saline (Hespan) and 6% HES 450/0.7 in lactated Ringer's solution (Hextend) have the same inhibition of the intrinsic coagulation pathway and platelet function. Multiple studies have suggested that 6% Hespan inhibits coagulation and increases chest tube drainage and transfusion requirements in cardiac surgical patients. There have been few studies of the effects of 6% Hextend, a relatively new plasma volume expander, on coagulation and the results thus far have been mixed. DESIGN: A prospective in vitro study. SETTING: A large academic medical center. PARTICIPANTS: Blood was collected from 30 healthy volunteers. Interventions : The blood was fractionated and diluted by 30% with Hextend, Hespan, normal saline, and lactated Ringer's solutions, with a native sample for a control. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were thromboelastography and activated partial thromboplastin time (APTT). For each of the TEG parameters, there was no difference between samples diluted with Hextend compared with Hespan (p > or = 0.112 in all cases). APTT did not differ significantly between samples diluted with Hextend compared with Hespan (p = 0.562). CONCLUSIONS: This prospective in vitro study suggests that Hextend and Hespan, hydroxyethyl starch 450/0.7 in different base solutions, exhibit the same effect on platelet function as measured by the TEG.     

Artificial colloids impair haemostasis. An in vitro study using thromboelastometry coagulation analysis

BACKGROUND: Hydroxyethyl starch (HES) solutions impair haemostatic mechanisms. The impact of the degree of substitution (DS) of a HES solution on thromboelastometry tracings is unclear. Therefore we tested the hypothesis of whether the DS has an effect on the haemostatic defect caused by HES, and assessed whole blood coagulation by thromboelastometry coagulation analysis (ROTEM, Pentapharm Co., Munich, Germany) in serial in vitro haemodilutions of colloids. METHODS: Whole blood was withdrawn from 12 volunteers in a crossover study. Six per cent low-molecular weight HES with a high (HES MW 120 kDa/degree of substitution 0.7) and low (HES MW 130 kDa/0.4) degree of substitution, 4% succinylated gelatin (GEL) or 4% albumin (ALB) was added to citrated venous whole blood samples to make 20, 40, 60 vol.% end-concentrations of each of the solutions. Samples were analyzed by ROTEM. RESULTS: There was a comparable decrease in maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF/(100-MCF)] by HES 120/0.7 and HES 130/0.4 at 20 and 40 vol.% dilutions. At 60 vol.% dilution HES 120/0.7 decreased less alpha-angle and MCF than HES 130/0.4 (P < 0.05). With moderate dilutions all colloids shortened coagulation time (CT). At 20, 40 and 60 vol.% dilutions MCF and G were more decreased in both HES groups than in the ALB and GEL groups (P < 0.05). Furthermore, at 40 and 60 vol.% dilutions G deteriorated more in the GEL than in the ALB group (P < 0.05). CONCLUSION: In vitro the impact of the degree of substitution of HES solution on thromboelastometry coagulation analysis was modest. Haemodilution with gelatin and albumin induced fewer coagulation abnormalities than HES. In addition, the haemodilution with gelatin impaired coagulation more than albumin solution.     

Effects of plasma substitutes on hemostasis

OBJECTIVE: Data synthesis on haemostasis effects of cristalloids and colloids and clinical implications for their use for plasma volume replacement. DATA SOURCES: Data were searched in the Medline database from 1954 to 2000 using the following key-words: cristalloids, colloids, albumin, gelatin, dextran, hydroxyethyl starch, haemostasis, von Willebrand disease, haemodilution. DATA EXTRACTION: Publications from 1954 to 1990 were selected depending on the quality of their methodology. Most of articles published after 1990 and all types including case report were accepted. DATA SYNTHESIS: Cristalloids induces a moderate hypercoagulable state with 10 to 30% haemodilution. Hypocoagulation is observed above 50% haemodilution. Albumin does not impair hemostasis except with a 50% or more haemodilution where hypocoagulation is observed. Dextran dramatically impairs haemostasis and fibrinolysis. With increasing dose, a progressive decrease of all von Willebrand multimers, mostly the largest, is observed. Till 50% haemodilution, gelatin has a moderate impact on hemostasis, but platelet aggregation is moderately modified. However this moderate impairment of haemostasis may potentiate the haemostatic effect of other colloids when used in association with gelatin. More than 30% haemodilution with hydroxyethyl starch (HES) has a serious effect in vitro on platelet function and fibrinoformation. In most studies in human, less than 20 ml.kg-1 plasma volume replacement has no clinical impact, but in some evaluations postoperative bleeding is more important with HES, particularly HES 450, in comparison to other colloids. With HES 450 and HES 200 highly substituted (0.6 of degree of substitution) intravascular cumulation of large molecules leads to type I von Willebrand syndrome when doses overtake 80 ml.kg-1. Dextran and HES are prohibited in patients with impaired haemostasis due to congenital disease (haemophilia and von Willebrand disease) or acquired defect (thrombocytopenia). Caution is required in patients with renal failure or receiving antithrombotic or non-steroidal anti-inflammatory agents. Patients without a haemorrhagic diathesis must not received more than 1.5 g.kg-1.j-1 of dextran and restrictive conditions of use must be respected with HES. CONCLUSION: Except isotonic cristalloids, all colloids induce haemostastic changes particularly for haemodilution over 30%. Effects are more pronounced with HES and dextran.     

Inhibition of platelet function by hydroxyethyl starch solutions in chronic pain patients undergoing peridural anesthesia

The use of hydroxyethyl starch (HES) solutions as a fluid replacement before peridural blockade may compromise blood coagulation, thus increasing the risk of neuraxial bleeding. In this prospective, double-blind, placebo-controlled, crossover study, we compared the influence of HES 130 (molecular weight in kilodalton), HES 200, and lactated Ringer's solution on platelet function and hemodynamics in chronic low back pain patients scheduled for peridural blockades. Patients received 3 test infusions of 10 mL/kg each administered IV for 30 min. Collagen/epinephrine and collagen/adenosine diphosphate were used as agonists for assessment of platelet function analyzer-closure times. Arterial blood pressure, heart rate, platelet counts, and hemoglobin levels were documented. Platelet function analyzer-closure times remained stable after lactated Ringer's solution but were significantly prolonged after HES. The platelet-inhibiting effect of HES 200 was more than that of HES 130. Hemodynamic stability was sufficiently maintained by all test infusions. In contrast to previous observations, a relevant antiplatelet effect of both low and medium molecular weight HES solutions was found in this study in chronic pain patients undergoing peridural anesthesia. Because hemostasiological competence is a prerequisite for safe neuraxial blockade, the decision of HES for intravascular fluid administration before blockade should be critically made.     

剖宫产术前急性高容量血液稀释对产妇高凝状态的影响

目的 观察羟乙基淀粉(HES)术前急性高容量血液稀释(AHHD)对剖宫产产妇高凝状态的影响.方法 择期行剖宫产的产妇40例,随机均分为两组.术前30 min内输注15 ml/kgHES 200/0.5(H组)或复方乳酸钠(RL)(R组).抽取静脉血标本,采用血栓弹力描记仪检测麻醉前(T0)、AHHD结束后即刻(T1)、1 h(T2)、4 h(T3)时的凝血状态.结果 与T0比较,H组与R组产妇的TEG参数R值在T1时明显延长(P＜0.05);H组的TEG参数ANG、MA、CI在T1、T2、T3时明显减小(P＜0.05),R组仅在T3时明显增加(P＜0.05).与R组比较,H组在T1～T3时的TEG参数ANG、MA、CI明显减小(P＜0.05).结论 剖宫产术前采用HES 200/0.5行AHHD能减轻剖宫产围术期产妇的高凝状态,对预防术后静脉血栓形成可能有一定的作用.     

Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo

BACKGROUND: The study was conducted to explore the effects of colloid and crystalloid solutions on activation of fibrinolysis during orthopaedic surgery and to determine whether fluids facilitate clot dissolution at a particular fibrinolytic activity. METHODS: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured in plasma samples of 66 orthopaedic patients randomly receiving gelatin solution, hydroxyethyl starch (HES) (130/0.4), or exclusively Ringer's lactate solution. Plasma obtained before induction of anaesthesia (undiluted) and at the end of surgery (diluted) was exposed to recombinant tissue plasminogen activator (r-tPA) in vitro and analysed by modified thrombelastography (ROTEM). RESULTS: There were similar changes in t-PA and PAI-1 concentrations in the gelatin, HES, and Ringer's lactate groups. When compared with the effect of r-tPA on undiluted plasma samples, the presence of colloids prompted faster clot dissolution than did Ringer's lactate solution. Lysis index at 30 min decreased significantly [median (min/max); P vs Ringer's lactate solution] to 43 (1/82)% (P=0.007), 14 (3/70)% (P<0.001), and 91 (34/97)%, lysis onset time decreased to 1269 (1054/1743) s (P=0.007), 972 (490/1565) s (P<0.001), and 1970 (1260/2165) s, and lysis time to 2469 (1586/3303) s (P=0.019), 2002 (1569/3600) s (P=0.006), and 3012 (2017/3600) s in the gelatin, HES, and Ringer's lactate groups, respectively. CONCLUSIONS: The type of i.v. fluid used does not influence endogenously occurring fibrinolytic activity in patients undergoing major orthopaedic surgery. However, during hyperfibrinolysis, the presence of HES or gelatin solution facilitates clot disintegration to a greater extent than Ringer's lactate solution, because the weaker clots formed with colloids dissolve faster.     

Influence of fluid infusion associated with high-volume blood loss on plasma propofol concentrations

BACKGROUND: It is common clinical practice to use fluid infusion to manage high-volume blood loss until a blood transfusion is performed. The authors investigated the influence of fluid infusion associated with blood loss on the pseudo-steady state propofol concentration. METHODS: Twenty-seven swine were assigned to a lactated Ringer's solution group, a hydroxyethyl starch group, or a threefold lactated Ringer's solution group (n = 9 in each group). After 180 min of steady state infusion of propofol at a rate of 2 mg.kg(-1).h(-1), hemorrhage and infusion were induced by stepwise bleeding followed by fluid infusion every 30 min. In each of the first two steps, 400 ml blood was collected; thereafter, 200 ml was collected at each step. Just after each bleeding step, fluid infusion was rapidly performed using a volume of lactated Ringer's solution or hydroxyethyl starch equivalent to the blood withdrawn, or a threefold volume of lactated Ringer's solution. Hemodynamic parameters and the plasma propofol concentration were recorded at each step. RESULTS: Although the plasma propofol concentration in the lactated Ringer's solution group increased with hemorrhage and infusion, it decreased in both the hydroxyethyl starch and the threefold lactated Ringer's solution groups. The propofol concentration in the hydroxyethyl starch group could be expressed by the following equation: Plasma Propofol Concentration Decrease (%) = 0.80 x Hematocrit Decrease (%) (r2 = 0.83, P < 0.0001). CONCLUSIONS: When high-volume blood loss is managed by isovolemic hemodilution, the plasma propofol concentration during continuous propofol infusion decreases linearly with the hematocrit decrease.     

羟乙基淀粉130/0.4和琥珀酰明胶对SICU患者毛细血管通透性及炎性反应的影响

目的研究羟乙基淀粉130/0.4和琥珀酰明胶对SICU患者毛细血管通透性及炎性反应的影响。方法全麻下行胸腔或腹部手术、失血量超过400ml、术后即入SICU患者100例,年龄50～64岁,体重50～75kg,ASAⅡ级,随机分成5组,每组20例,各组术中分别静脉输注羟乙基淀粉130/0.4 500ml或1 000ml,琥珀酰明胶500ml或1 000ml及乳酸钠林格氏液10ml·kg~(-1)·h~(-1),术后收入SICU。分别于术前、术后入SICU 6h时留取尿液标本,采用ELISA法测定尿白蛋白浓度,酶比色法测定尿肌酐;计算尿白蛋白/尿肌酐比值(MA/CR);抽取10ml深静脉血,采用ELISA法测定血浆IL-6浓度。结果术中静脉输注羟乙基淀粉130/0.4和琥珀酰明胶的MA/CR较静脉输注乳酸钠林格氏液降低(P<0.05);术中输注相同容积羟乙基淀粉和琥珀酰明胶的MA/CR差异无统计学意义(P>0.05);各组入SICU6h时血浆IL-6水平较术前明显升高(P<0.05),5组血浆IL-6水平差异有统计学意义,其中术中静脉输注羟乙基淀粉的最低(P<0.05)。结论静脉输注羟乙基淀粉130/0.4或琥珀酰明胶500 ml有助于改善SICU患者毛细血管的通透性,而羟乙基淀粉130/0.4的抗炎作用明显优于琥珀酰明胶。     

Coagulation effects of a recently developed hydroxyethyl starch (HES 130/0.4) compared to hydroxyethyl starches with higher molecular weight

BACKGROUND: Hydroxyethyl starches (HES) are known to interfere with blood coagulation according to molecular weight, the degree of substitution and the C2/C6 ratio. A recently developed low molecular hydroxyethyl starch (HES 130/0.4) was designed to reduce the blood compromising potency. METHODS: In this study, effects of a 30% in vitro haemodilution with the new HES preparation (HES 130/0.4) in comparison to HES 200/0.5, HES 450/0.7 and sodium chloride solution were investigated using intrinsic and extrinsic activated thrombelastography (TEG) and plasmatic coagulation tests. RESULTS: Whereas plasmatic tests revealed no prolongation of coagulation by HES in comparison to sodium chloride, the TEG variables clotting time, clot formation time and maximal clot firmness showed a significant (P<0.05) inhibition by all the HES preparations. The inhibition was most pronounced in HES 450 (P<0.05 vs HES 130) while HES 130 did not show a statistically significant difference in extrinsic activated maximal clot firmness when compared to sodium chloride. CONCLUSION: These in vitro results demonstrate that hydroxythyl starches especially compromise clot polymerisation. The new preparation HES 130/0.4 seems to inhibit platelet function to a lesser extent than hydroxyethyl starch preparations with a higher molecular weight and degree of substitution.     

Hydroxyethyl starch impairs in vitro coagulation

Background: Artificial colloids affect haemostasis. Particularly hydroxyethyl starch (HES) solutions may have detrimental effects on haemostatic mechanisms.
Methods: In a crossover study blood was withdrawn from ten volunteers. Ringer's acetate, 6% low molecular weight HES (M_w 120 000/molar substitution ratio 0.7), 10% low molecular weight HES M_w 200 000/0.5) and 6% high molecular weight HES (M_w 400 000/0.7) or 4% albumin was added to venous blood samples to make either 20 vol.% or 50 vol.% concentrations of each of the solutions. Samples were analyzed by thrombelastography (TEG).
Results: All HES solutions at 20 vol.% concentration impaired haemostasis as demonstrated by decreased clot formation rate (α-angle and maximum amplitude (MA)). In contrast, Ringer's acetate and albumin improved coagulability at 20 vol.% concentrations. Coagulation time (r+K) was prolonged at 50 vol.% dilutions of all solutions. The median r+K was greater with HES 400 ( P <0.05) and HES 200 (N. S.) than with HES 120.
Conclusion: We conclude that HES at 20 and 50 vol.% concentrations has an adverse effect on in vitro measures of coagulation. A 50% dilution with high molecular weight HES seems to impair coagulation more than low molecular weight HES. Ringer's acetate and albumin caused a hypercoagulable state at a concentration of 20 vol.%, but the higher concentration decreased coagulability.     

The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery

PURPOSE: Fluid preloading with colloids reduces hypotension after spinal anesthesia for Cesarean delivery more effectively than crystalloids. However, the effects of fluid preloading regimens on coagulation in pregnant patients remain unresolved. The aim of this study was to compare the effects on coagulation of fluid preloading with 6% hydroxyethyl starch (HES) and lactated Ringer's (LR) solution using thromboelastography (TEG) with kaolin-activated whole blood in healthy pregnant patients prior to spinal anesthesia for Cesarean delivery. METHODS: After obtaining Ethics committee approval, 30 parturients were prospectively randomized prior to spinal anesthesia for elective Cesarean delivery to receive fluid preloading with either 1500 mL LR or 500 mL 6% HES over 30 min. Thromboelastography was performed immediately prior to and after fluid preloading. Standard TEG parameters were analyzed in terms of r time (min), k time (min), alpha angle (degrees) and maximum amplitude (mm). RESULTS: Group HES had statistically significant longer reaction times (r) and clot formation times (k) after fluid loading compared to baseline values (P < 0.05 respectively), although these post-fluid loading TEG parameters remained within a normal reference range. No significant differences in TEG values were seen after preloading within the LR group. CONCLUSION: Fluid preloading with 500 mL 6% HES in healthy parturients produced mild coagulation effects, as measured with TEG, prior to spinal anesthesia for Cesarean delivery. No significant effects on coagulation with TEG were observed following preloading with 1500 mL LR.     

Colloids versus crystalloids and tissue oxygen tension in patients undergoing major abdominal surgery

The effects of intravascular volume replacement regimens on tissue oxygen tension (ptiO(2)) are not definitely known. Forty-two consecutive patients scheduled for elective major abdominal surgery were prospectively randomized to receive either 6% hydroxyethyl starch (HES) (mean molecular weight 130 kd, degree of substitution 0.4, n = 21) or lactated Ringer's solution (RL, n = 21) for intravascular volume replacement. Fluids were administered perioperatively and continued for 24 h on the intensive care unit to keep central venous pressure between 8 and 12 mm Hg. The ptiO(2) was measured continuously in the left deltoid muscle by using microsensoric implantable partial pressure of oxygen catheters after the induction of anesthesia (baseline, T0), 60 min (T1) and 120 min thereafter (T2), at the end of surgery (T3), and on the morning of the first postoperative day on the intensive care unit (T4). HES 130/0.4 2920 +/- 360 mL and 11,740 +/- 2,630 mL of RL were given to the patients within the study period. Systemic hemodynamics and oxygenation (PaO(2), PaCO(2)) did not differ significantly between the two volume groups throughout the study. From similar baseline values, ptiO(2) increased significantly in the HES-treated patients (a maximum of 59% at T4), whereas it decreased in the RL group (a maximum of -23% at T4, P < 0.05). The largest differences of ptiO(2) were measured on the morning of the first postoperative day. We conclude that intravascular volume replacement with 6% HES 130/0.4 improved tissue oxygenation during and after major surgical procedures compared with a crystalloid-based volume replacement strategy. Improved microperfusion and less endothelial swelling may be responsible for the increase in ptiO(2) in the HES 130/0.4-treated patients. IMPLICATIONS: In patients undergoing major abdominal surgery, a colloid-based (with hydroxyethyl starch [HES] 130/0.4) and a crystalloid-based (with lactated Ringer's solution [RL]) volume replacement regimen was compared regarding tissue oxygen tension (ptiO(2)) measured continuously by microsensoric implantable catheters. The ptiO(2) increased in the HES-treated (+59%) but decreased in the RL-treated (-23%) patients. Improved microcirculation may be the mechanism for the better ptiO(2) in the HES group.     

Thrombelastographic coagulation analysis following in vitro and in vivo haemodilution with hydroxyethyl starch (HES)

In the study presented the effects of in vitro hemodilution with HES on coagulation are compared with the effects of in vivo hemodilution using thrombelastography (TEG). The in vivo hemodilution was performed by the i. v. infusion of 1000 ml 6 % solution of hydroxyethyl starch HES (2 formulations with HES 130/0.4 and one formulation with HES 200/0.5) in healthy volunteers during 30 min. The in vitro hemodilution was performed with blood samples taken from the volunteers before the infusion was started. These samples were diluted with HES-solution until the same hemoglobin concentration measured at the end of the infusion was attained. The in vivo TEG-parameters remained in the reference range of the method, however all in vitro TEG-parameters are out of the range of normal values. The isolated interpretation of the in vitro data shows an impairment of blood coagulation. The shortening of the reaction time as an indicator for the initiation of blood clotting points to activated coagulation by in vivo hemodilution with HES, whereas in vitro the prolongation of the reaction time is indicative for retardation of clotting. The evaluation of the TEG-parameters and of other clotting parameters determined prior to the beginning of the infusion, at the end of the infusion and four hours after termination of the infusion of HES 130/0.4 and of HES 200/0.5 to healthy volunteers show alterations of blood coagulation parameters caused mainly by dilutional effects. The more pronounced alterations found in vitro cannot be interpreted as impairment of haemostasis in vivo. On the other hand, the likewise haemodilution in vitro causes an impairment of coagulation. Therefore, the effects of in vitro hemodilution with HES on coagulation differ qualitatively and quantitatively from the effects of in vivo hemodilution.     

Hydroxyethyl starch (HES) 130/0.4 provides larger and faster increases in tissue oxygen tension in comparison with prehemodilution values than HES 70/0.5 or HES 200/0.5 in volunteers undergoing acute normovolemic hemodilution

Stable hemodynamics and improved rheology are important effects of hemodilution with hydroxyethyl starch (HES) infusions. One clinical indicator of improved rheology is increased tissue oxygen tension (tpO(2)). In this prospective, randomized, double-blinded, crossover study, we examined the effects of acute normovolemic hemodilution with HES 130/0.4 on hemodynamics and skeletal muscle tpO(2) in comparison with conventional HES solutions. Twelve healthy volunteers were randomly enrolled in each group. At an interval of >8 days, volunteers donated 18% of their calculated blood volume within 30 min and randomly received 6% HES 130/0.4, 6% HES 70/0.5, or 6% HES 200/0.5 (crossover design) in a 1:1.2 ratio to their blood loss. Hemodynamic variables, tpO(2) in the quadriceps muscle, hematocrit, plasmatic HES concentrations, plasma viscosity, colloid osmotic pressures, and platelet aggregation were measured until 6 h after the infusion of HES. No differences were found among groups with respect to changes of hemodynamics, hematocrit, or platelet aggregation. With HES 200, colloid osmotic pressures and plasma viscosities were larger than after HES 70 (P < 0.05). HES 130 in comparison with HES 70 and 200 caused the fastest (30 min versus 90 min and 150 min after hemodilution; P < 0.05) and largest increase of tpO(2) in comparison to baseline (+93% versus +33% and 40%; P < 0.05). In healthy volunteers undergoing acute normovolemic hemodilution, the newly designed HES 130/0.4 showed a more pronounced and earlier increase of skeletal muscle tpO(2) in comparison with prehemodilution values than HES 70/0.5 or 200/0.5. IMPLICATIONS: The effects of three different hydroxyethyl starch (HES) solutions on hemodynamics, rheology, and skeletal muscle tissue tension after acute normovolemic hemodilution were examined in awake volunteers. With HES 130/0.4, increases of tissue oxygen tension in comparison to baseline were larger and more rapid than with HES 70/0.5 or HES 200/0.5.     

A head-to-head comparison of the in vitro coagulation effects of saline-based and balanced electrolyte crystalloid and colloid intravenous fluids

Both fluid composition (e.g., type of hydroxyethyl starch) and formulation (e.g., saline or balanced salt carrier solution) may alter whole blood coagulation. We therefore enrolled 10 healthy volunteers to test ex vivo, thrombelastograph-based blood coagulation differences of eight crystalloid and colloid solutions at 20%, 40%, and 60% dilutions. Saline and lactated Ringer's solution produced a hypercoagulable state at 20%-40% dilutions. Saline, hetastarch in saline, pentastarch in saline, tetrastarch in saline, and human albumin solutions all produced a hypocoagulable state at 60% dilution. Hetastarch in saline also produced a hypocoagulable state at 40% dilution. The larger molecular weight starches produced more intense coagulation abnormalities than the medium molecular weight compounds formulated similarly (i.e., suspended in saline or balanced salt solution). The balanced salt solutions caused fewer coagulation abnormalities, especially pentastarch in balanced salt solution. This balanced salt pentastarch preparation produced the least derangement of coagulation of the colloid solutions at all dilutions, causing hypercoagulability at the lower dilutions and minimal coagulation derangement at 60% dilution. These data support the theory that smaller molecular weight hydroxyethyl starches and colloids suspended in balanced salt solutions preserve coagulation better than large molecular weight starches and saline-based colloids, as judged by thrombelastography.